This figure presents an MRI image of the human brain showing from different contrasts, each highlighting different structures in the brain.

WP1 MPI CBS: In vivo qMRI imaging


Prof. Dr. Nikolaus Weiskopf leads the Department of Neurophysics at the MPI CBS, Leipzig, Germany, which focuses on the development of novel methods for non-invasive MRI-based histology. This approach combines advanced MRI acquisition methods with biophysical models and multimodal atlases in order to glean information on tissue microstructure from macroscopically measured MR parameters.

Advanced MRI acquisition: Weiskopf group developed a method that records intrinsically co-localized multiple quantitative parameters maps (MPM) of MR parameters (longitudinal (R1) and effective transverse relaxation rates (R2*), magnetisation transfer (MT), proton density,  QSM) with submillimetre resolution (400 µm isotropic) in vivo at 7T using prospective motion correction (PMC). MPMs are sensitive probes of tissue microstructure reflecting brain myelination (R1, R2*,  QSM), brain iron accumulation(R2*, QSM) and tissue water content (PD, R1, R2).  The ultra-high resolution and unique combination of multiple parameters promises quantitative information about the small nuclei in SN and LC in PD (Fig. 1 A, B).  Compared to conventional weighted MRI images, MPMs provide sensitive and specific metrics to follow subtle changes in brain microstructure induced by healthy aging or neurodegeneration in longitudinal studies.

Biophysical models: The group recently further enhanced method specificity by developing and validating advanced biophysical models of MPMs based on quantitative histological information of cellular iron distribution in SN, which quantitatively links MRI parameters to cellular iron distribution. These models relate MPMs, at ultra-high but still mesoscopic resolution, to maps of microscopic distributions of iron-rich dopaminergic neurons in SN, and allows separation of neuromelanin and ferritin iron pools strongly improving MRI specificity. Based on this model, the group proposed a unique quantitative biomarker of dopaminergic cellular density in nigrosome 1 based on combination of R2 and R2* maps, which will be implemented and tested in vivo within IronSleep.

Multimodal atlases: Imaging small subcortical nuclei is challenging due to their small size and complex anatomy. Particularly dopaminergic nigrosomes and the noradrenergic LC are millimetre to submillimetre sized and require the currently maximal MRI resolution in vivo. Therefore, neuroanatomical reference data is required to guide MRI data analysis and interpretation. In collaboration with Dr. Alkemade and her team, Weiskopf group recently contributed to a unique dataset bridging histology and in vivo MRI by combining ultra-high resolution MPMs with 3D multimodal histology on three post-mortem human brains.

IronSleep working plan

Within IronSleep we will implement an MR-based method for in vivo microstructural mapping of brain stem nuclei with submillimeter resolution. For this purpose we will combine advanced ultrahigh resolution MRI acquisition using PMC with the recently developed biophysical models of MR contrast in subcortical nuclei. Informed by the cellular iron distribution from our previous work and anatomical atlases developed in WP2 we will establish optimal imaging protocol for microstructural brain stem mapping. Our method will rely on a novel combination of two biophysical phenomena: i) the effect of neuromelanin-bound iron on the longitudinal relaxation rate (R1) and magnetization transfer (MT) rates of water protons; ii) the distinct contribution of iron-rich dopaminergic cells to R2 and R2* and QSM contrast.

Team – MPI CBS

Professor Dr Nikolaus Weiskopf

Professor Dr Nikolaus Weiskopf

Nikolaus Weiskopf is an expert in magnetic resonance imaging (MRI) methods and their application to neuroimaging. He develops methods for characterization of functional and anatomical microstructure (i.e. in-vivo histology) using advanced MRI acquisition, biophysical modeling and post-mortem/in-vivo validation. He studies microstructural structure-function relationships and plasticity, including in clinical trials (e.g. He is Associate Editor of the Frontiers in Brain Imaging Methods journal, Editor for NBDT and regularly serves as reviewer and/or advisor for large multi-center studies and neuroimaging centers (e.g. UK Biobank Imaging Extension, German National Cohort, Leibniz Institute for Neurobiology).
Dr Evgeniya Kirilina

Dr Evgeniya Kirilina

Research group leader
I am a physicist working in the field of brain research. I aim to uncover crucial mechanisms of human brain aging, by identifying the contribution of iron accumulation, a major determinant of brain development and brain decline. To do so, my group develops new specific and sensitive markers for the cellular distribution and the chemical form of iron by integration of cutting-edge MRI with advanced histology and biophysical models. We combine the recent improvement of advanced high-field MRI, latest progress in the understanding of brain iron biochemistry and biophysical modeling to achieve novel MRI brain iron markers with cellular sensitivity. Our goal is to contribute to a mechanistic understanding of the brain iron metabolism and its role in brain development to enable new diagnostics and therapies targeting iron induced neurodegeneration in the future.

Dr Kerrin Pine

Scientific researcher
Kerrin Pine is a senior physicist developing methods to characterize and quantify human cortical microstructure using high-resolution MRI. Working in the Neurophysics department of Prof. Nikolaus Weiskopf, he is responsible for advanced MRI acquisitions including pulse sequence programming and prospective motion correction across a range of MRI platforms (Terra, Connectom and Prisma) and imaging centres. He participates in international ultrahigh field networks and regularly serves as reviewer for leading journals.
Malte Brammerloh

Malte Brammerloh

Doctoral researcher
Malte Brammerloh is a Ph.D. student working on biophysical models of iron-induced MRI relaxation in the brain to foster more accurate MRI interpretation. He leverages quantitative 3D iron histology, using proton-induced X-ray emission and X-ray fluorescence microscopy, and ultra-high field post mortem and in vivo MRI to develop quantitative iron markers in the substantia nigra. As first author, he published two papers (NeuroImage and Radiology) and five ISMRM abstracts, which were honored with two Magna Cum Laude and one Summa Cum Laude awards. He was awarded the third rank Gorter price from the German Section of the ISMRM and won a second prize at the quantitative MR study group awards. His Ph.D. supervisors are Evgeniya Kirilina and Nikolaus Weiskopf.


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